title: A Kampo (traditional Japanese herbal) medicine, Hochuekkito, pretreatment in mice prevented influenza virus replication accompanied with GM-CSF expression and increase in several defensin mRNA levels.
abstract: A Kampo medicine, Hochuekkito (TJ-41), with an influenza virus-preventing effect had life-extending effectiveness, and immunological responses other than interferon (IFN)-α release were examined. TJ-41 (1 g/kg) was given to C57BL/6 male mice orally once a day for 2 weeks. Mice were then intranasally infected with influenza virus. After infection, virus titers and various parameters, mRNA levels and protein expression, for immunoresponses in the bronchoalveolar lavage fluid or removed lung homogenate, were measured by plaque assay, quantitative RT-PCR and ELISA. IFN-α and -β levels of TJ-41-treated mice were higher than those of the control. Toll-like receptor TLR7 and TLR9 mRNAs were elevated after infection, but retinoic acid-inducible gene (RIG-1) family mRNA levels, RIG-1, melanoma differentiation-associated gene 5 and Leishmania G protein 2 showed no response in either TJ-41 or control groups. Interferon regulatory transcription factor (IRF)-3 mRNA levels to stimulate type I (α/β) IFN were increased, but IRF-7 did not change. Only granulocyte-macrophage colony-stimulating factor (GM-CSF) after Hochuekkito treatment was significantly elevated 2 and 3 days after infection. The mRNA levels of 7 defensins after infection increased compared to preinfection values. The key roles of TJ-41 were not only stimulation of type I IFN release but also GM-CSF-derived anti-inflammation activity. Furthermore, defensin (antimicrobial peptide) mRNA levels increased by infection and were further enhanced by TJ-41 treatment. Defensin might prevent influenza virus replication.
authors.affiliation: Collaborative Research Resources, Core Instrumentation Facility, Keio University School of Medicine, Tokyo, Japan. kdanmrw@sc.itc.keio.ac.jp
authors.forename: Katsuaki
authors.initials: K
authors.lastname: Dan
authors.forename: Hiroko
authors.initials: H
authors.lastname: Akiyoshi
authors.forename: Kaori
authors.initials: K
authors.lastname: Munakata
authors.forename: Hideki
authors.initials: H
authors.lastname: Hasegawa
authors.forename: Kenji
authors.initials: K
authors.lastname: Watanabe
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D002460:Cell Line; D016207:Cytokines / Q000276:immunology; D023082:Defensins / Q000235:genetics; D004285:Dogs; D004365:Drugs, Chinese Herbal / Q000494:pharmacology / Q000627:therapeutic use*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000276:immunology; D053118:Influenza A Virus, H1N1 Subtype / Q000187:drug effects* / Q000502:physiology; D008168:Lung / Q000187:drug effects / Q000276:immunology; D008297:Male; D020835:Medicine, Kampo; D051379:Mice; D008810:Mice, Inbred C57BL; D009976:Orthomyxoviridae Infections / Q000188:drug therapy* / Q000276:immunology; D012333:RNA, Messenger / Q000378:metabolism; D014779:Virus Replication / Q000187:drug effects
chemical_list: D000998:Antiviral Agents; D016207:Cytokines; D023082:Defensins; D004365:Drugs, Chinese Herbal; D012333:RNA, Messenger; C402943:bu-zhong-yi-qi-tang; D016178:Granulocyte-Macrophage Colony-Stimulating Factor